Tissue or organ damage, dysfunction, or loss is a feature of a wide variety of medical conditions. In some such conditions replacement of the damaged tissue or organ is the best or even the only option.
For example, oesophageal atresia is a congenital medical condition which affects the alimentary tract and which occurs in approximately 1 in 2500 live births. It causes the oesophagus to end in a blind-ended pouch rather than connecting normally to the stomach. The most severe case of oesophageal atresia is sometimes referred to as oesophageal agenesis, where no oesophagus is present at all. The most immediate and effective treatment in the majority of cases is a surgical repair to reconnect the two ends of the oesophagus to each other.
Transplantation from human donors (either live or cadaveric) has enjoyed significant success, and procedures such as liver, heart, and kidney transplants are becomingly increasingly common. However, the severe shortage of donors, the complexity of harvesting organs and delivering them to the recipient, and the potential for transmission of infectious agents are significant shortcomings of this approach, as are its applicability to pediatric patients.
As explained in, for example, WO0214480, tissue engineering is an evolving field that seeks to develop techniques for culturing replacement tissues and organs in the laboratory.
The general strategy for producing replacement tissues utilizes mammalian cells that are seeded onto an appropriate substrate for cell culture. The cells can be obtained from the intended recipient (e.g., from a biopsy), in which case they are often expanded in culture before being used to seed the substrate. Cells can also be obtained from other sources (e.g., established cell lines). After seeding, cell growth is generally continued in the laboratory and/or in the patient following implantation of the engineered tissue.
Thus, for example, developing a construct for regeneration or substitution of damaged luminal organs (such as the oesophagus) needs a combination of scaffold and cells to produce a functional three dimensional tissue.
WO0214480 (the disclosure of which is incorporated herein by reference) describes methods for producing a tissue engineered construct by growing cells in vitro on a substrate and then decellularizing the construct to produce a decellularized construct consisting largely of extracellular matrix components. It is reported that the construct can be used immediately or stored until needed. The decellularized construct can be used for further tissue engineering, which may include seeding the construct with cells obtained from the intended recipient of the construct. During any of the growth phases required for production of the construct, the developing construct may be subjected to various tissue engineering steps such as application of mechanical stimuli including pulsatile forces. The methods also include producing an engineered native tissue by harvesting tissue from an animal or human, performing one or more tissue engineering steps on the tissue, and subjecting the tissue to decellularization. The decellularized, engineered native tissue may then be subjected to further tissue engineering steps
WO2003092471 (also published as US2005/0202058) describes tissue graft constructs that include an extracellular matrix material in combination with added endothelial cells and at least one additional added exogenous cellular population.
US2014/0341862 relates to a method for preparing a tissue construct for medical purposes which uses endothelial progenitor cells (EPC) which have not been passaged multiple times and have a content of EOEC (early outgrowth endothelial progenitor cells) and LOEC (late outgrowth endothelial progenitor cells). These cells and fibroblasts and/or muscle cells, viz. myoblasts, myofibroblasts, smooth muscle cells or the progenitors thereof, are, in the form of living cells, seeded onto a matrix or introduced into a matrix in order to yield the tissue construct following further treatment steps. The matrix is preferably a protein preparation, more particularly a fibrinogen preparation.
US 2004/0028662 relates to a cell colonisation process whereby biological cells are colonised on an synthetic or natural tissue matrix in order to obtain a tissue implant or tissue transplant. The growth of the cells is promoted by the addition of mediators, factors or co-factors supplied by co-cultivated cells.
WO03/095631 relates to multipotent stem cells, methods for their isolation and in vitro expansion, processes for their in vitro differentiation, and their use for regenerating or repairing biological tissues.
Unfortunately, existing approaches for cell seeding techniques and cell combinations in tissue engineering often show low cell engraftment and lack of a homogeneous population of cells on the scaffold. This inhibits the development of a functional tissue, particularly luminal tissue or organs.
Thus it can be seen that novel methods for seeding scaffolds of matrices for producing implantable luminal tissue or organs with improved cell engraftment or related properties would provide a contribution to the art.